Numerous reports have documented a markedly increased incidence of disordered mineral metabolism and bone changes of osteomalacia in patients on chronic anticonvulsant drug therapy. Recent studies from our laboratory have demonstrated (1) a significant incidence of hypocalcemia, reduced serum 25-hydroxycalciferol levels and osteopenia in patients on chronic anticonvulsant therapy and (2) definite drug-induced alterations in the in vivo and in vitro metabolism of vitamin D. The purposes of the proposed investigations will be (1) to employ the most sensitive available techniques, including serum vitamin D metabolite assays and photon absorption measurements of bone mineral content, to determine the incidence of and predisposing risk factors in the development of clinical evidence of disordered mineral metabolism in outpatients and institutionalized patients receiving chronic anticonvulsant or psychoactive drug therapy, (2) to quantitate the effects of treatment with these agents on the metabolism and biologic activity of vitamin D in man, (3) to assess the relative therapeutic effectiveness of vitamin D, 25OHD and 1,25(OH)2D in reversing drug-induced biochemical and histologic abnormalities, and (4) to explore through in vivo and in vitro animal studies the mechanisms whereby anticonvulsant drug administration alters the metabolism of mineral, vitamin D and bone. Specific areas to be investiaged include; the effects of drug type and dose, vitamin D and mineral intake, hepatic microsomal enzyme induceability, underlying disease state, activity level, age, sex and race on the development of clinical evidence of disordered mineral, vitamin D and bone metabolism in man; the nature of drug-induced alterations in the intracellular accumulation, distribution and metabolism of vitamin D and its metabolites; the individual and additive effects of drugs in inducing altered mineral and vitamin D metabolism; the specific effects of drugs on membrane transport of ions and bone formation; and the nature and biologic activity of drug-induced polar vitamin D, 250HD and 1,25(OH)2D metabolites.